title: Overcoming enzymatic resistance in bacteria: impact on future therapy.
abstract: Resistance of bacteria to antibiotics often involves inactivating enzymes. One approach developed to overcome this mechanism of resistance consists of combining an efficient but possibly unstable antibiotic with a powerful inhibitor of the inactivating enzyme. Attempts have been made with different antibiotics but significant success has only been obtained with the beta-lactams, clavulanic acid and sulbactam being the only compounds currently being used clinically. Sulbactam, a time-dependent irreversible inhibitor of plasmid-mediated penicillinases and of chromosomally mediated penicillinases and cephalosporinases, potentiates the antibacterial activity of beta-lactams but only exhibits a moderate antibacterial activity, which is related to its affinity for the lethal targets of the beta-lactams--the penicillin-binding proteins. In bacterial strains that produce either low amounts of beta-lactamase, or none at all, a synergistic effect can be observed when sulbactam is associated with a beta-lactam antibiotic that has a complementary affinity for the target sites.
authors.affiliation: National Museum of Natural History, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Labia
authors.forename: M
authors.initials: M
authors.lastname: Barthélémy
authors.forename: J
authors.initials: J
authors.lastname: Péduzzi
authors.forename: A
authors.initials: A
authors.lastname: Morand
authors.forename: K
authors.initials: K
authors.lastname: Tiwari
authors.forename: A
authors.initials: A
authors.lastname: Kazmierczak
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002701:Chloramphenicol / Q000737:chemistry / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000737:chemistry / Q000378:metabolism; D019818:Clavulanic Acid; D002969:Clavulanic Acids / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D004791:Enzyme Inhibitors; D013407:Sulbactam / Q000494:pharmacology*; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000145:classification* / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002969:Clavulanic Acids; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D002701:Chloramphenicol; D015500:Chloramphenicol O-Acetyltransferase; D001618:beta-Lactamases; D013407:Sulbactam